In its inaugural tranche of grants, Fund for Science and Technology funded Benaroya Research Institute (BRI) to support its biorepository infrastructure—an essential engine behind groundbreaking discoveries in human immunology—and to support the bioinformaticians who analyze the vast datasets derived from this resource. We sat down with BRI president Dr. Jane Buckner to learn more about the biorepository and the dedicated researchers working to conquer autoimmune diseases that afflict as many as 700 million people globally.
At a young age, Dr. Jane Buckner formed a hard and fast opinion about biology class– that it was tedious, unrelatable and nothing but memorization. She was more interested in creative pursuits, like playing the clarinet or exploring the outdoors. The curious nature she cultivated in her youth would find its way back into her professional life, and as it turns out, so would biology.
Biology became extremely relatable for Dr. Buckner, who received her MD from Johns Hopkins School of Medicine and now serves as president of Benaroya Research Institute (BRI). She continues to fuel her curiosity by running a lab dedicated to working with real patients – people experiencing autoimmune diseases who directly benefit from the power of bioscience research.
“Interactions with my patients inspired me to get into the lab and figure out what’s going on with autoimmune diseases,” Dr. Buckner recalled in making her start 30-plus years ago. “I always wanted to conduct research, specifically to learn more about my patients and their unique circumstances - ‘why’ they develop the disease and ‘how’ they respond to various treatments.”
Dr. Buckner’s affinity to investigate all things immunology and her connection to her patients contributed to what has become a world-class biorepository of blood and tissue samples that started 25 years ago and continues to unlock new immunological mysteries.
“The biorepository gives us a window into the human immune system both in healthy and disease states,” states Dr. Buckner with obvious pride. “It holds the answer to questions that I couldn’t have even imagined 25 years ago, or even 5 years ago. With so many technological breakthroughs on the immediate horizon, I believe these samples hold answers to some of our biggest questions, even those still to come.”
Just one example of the abundant success stories shared by Dr. Buckner was her team’s work studying regulatory T cells, trying to understand why they didn’t work in patients with type 1 diabetes, an autoimmune disease that impacts more than 1.6 million Americans. The answer they discovered was regulatory T cells actually do work in type 1 diabetes. Her group’s experiment, using biorepository blood, showed that aggressive immune cells (effector T cells) are no longer listening to immune regulators, which was the opposite of their hypothesis.
“I kind of love being wrong when research tells me what the right answer is,” said Dr. Buckner. “This discovery changed the way we approach type 1 diabetes and how to look at potential treatments.”
And she had another story (or four) to back that up.
"We were looking at what is called the IL-2 signaling pathway, an important regulator of the immune system’s response, in type 1 diabetes biorepository samples and we discovered the IL-2 pathway doesn’t work well,” explained Dr. Buckner. “So working with my colleague Dr. Carla Greenbaum, we decided that it made sense to give IL-2 as a therapy for type 1 diabetes. We tested this in a small group of participants to see if we could get some initial insight and, again, we were surprised because the dose of IL-2 we gave helped in some ways but also made things worse overall.”
Dr. Buckner recalls the “fun” that ensued: “While many clinicians were gearing up to start IL-2 therapy, our study made all of us rethink how we could use it – all due to a study with 10 people and samples from our biorepository.”
It was a speedy process, relative to research standards. “It was a 3-5 year period from our initial discovery about IL-2 using biorepository samples to conducting the trial intervention to me standing up in front of many scientists saying, ‘time out!’” She was also quick to point out that everyone in the 10-person study recovered.
One more story? This one involves ulcerative colitis that impacts more than 1 million Americans. A BRI research team read a study that found autoantibodies in a small group of ulcerative colitis patients. Autoantibodies are misdirected antibodies that attack the body instead of protecting it. In type 1 diabetes, autoantibodies are an important biomarker that precedes clinical diagnosis. They can be thought of as the “smoke” before “fire.” With that in mind, the research team pulled hundreds of samples from the BRI biorepository from people with ulcerative colitis and a subset of healthy controls. They found that nearly 100% of the patients with ulcerative colitis had this autoantibody, confirming the prior observation. “Not only is that amazing, but because we were using samples in the biorepository, this was accomplished in a matter of weeks as opposed to months or even years,” explained Dr. Buckner. “Now we hope to extend this work to develop ways to predict and prevent ulcerative colitis.”
Dr. Buckner speaks with enthusiasm about her team, along with every researcher and every employee at BRI. She describes BRI staff as driven by curiosity with a constant desire to move forward collaboratively, citing the repository as a foundation and powerful tool for that spirit of teamwork.
“Many of us are affected in one way or another by an autoimmune disease – be it personally or because of friends or family. We have dedicated our careers to helping people, so we take our work seriously and are driven to innovate,” she continued. “I’d say we’re driven by empathy as well.”
Perhaps many of the researchers at BRI were much like Dr. Buckner in her childhood – adventurous, out exploring nature, pushing boundaries, and nurturing an insatiable curiosity. Whatever brought them together, they are now exploring new territory in the complex cellular and genetic landscape of autoimmune diseases.
The BRI biorepository houses more than 350,000 samples with 16,000 active contributors across 11 different autoimmune diseases along with healthy control samples. This world-class repository dating back 25 years employs careful and consistent sample processing and storage protocols to ensure sample integrity. As a resource for global researchers, it allows scientists to dive into the causes of immune-mediated diseases and lights the path for potential prevention, faster diagnostics, and more effective treatment options.